ABSTRACT. Recent studies have revealed that the inflammatory process plays a role in the pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced glycation end products (RAGE) 11363 RAGE gene in osteoarthritis ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 11362-11370 (2015) participate in regulating inflammation, even in the production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1 have a marked effect on ligand binding and transcription regulating. In this study, we investigated the potential genetic contribution of the RAGE, S100A8, and MMP-1 genes to OA. We performed a matched case-control association study and genotyped OA patients and healthy controls, who were analyzed by polymerase chain reaction-restriction fragment length polymorphism assays. A total of 207 patients were diagnosed with knee OA and underwent total knee replacement. The control group included 207 individuals who had standard X-rays of the knee joints to confirm K/L < 2 and were matched by age and gender. Single-nucleotide polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8 rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant difference between OA patients and healthy controls. RAGE -429T/C and 557G/A showed a significant association between OA patients and healthy controls (P = 0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1 haplotypes showed associations with OA. Our results suggest that the investigated polymorphism in the RAGE gene play a role in OA in the Han Chinese population.

BackgroundDifferences between staged bilateral total knee replacement (TKR) and simultaneous bilateral TKR have been investigated, but few studies have investigated differences in the functional improvements resulting from these methods. Therefore, this study investigates the different functional improvements between staged bilateral total knee TKR and simultaneous bilateral TKR.MethodsAmong 144 potential bilateral TKR patients who were included in this study, 93 (64.6%) patients selected unilateral TKR and 51 (35.4%) selected bilateral TKR. Functional improvements were assessed using the Western Ontario and McMaster University osteoarthritis index (WOMAC) and the Medical Outcomes Trust Short Form-36 (SF-36), and patients were interviewed pre-operatively and after 6 months. A generalized equation was used to test for differences in functional improvements.ResultsAfter TKR, pain, stiffness, function and total WOMAC scores were significantly reduced in both groups, with mean changes from − 26.6 to − 41.4 and from − 27.5 to − 42.2.The mean health change of SF-36 scores, physical component and mental component scores changed to 45.2 ± 18.2, 74.0 ± 15.4 and 77.0 ± 9.6, respectively, in Group 1 and 47.1 ± 17.1, 74.0 ± 15.2 and 75.5 ± 12.1, respectively, in Group 2.Unilateral and simultaneous bilateral TKR produce similar functional improvements, although current work status may be a novel impact factor.ConclusionNo differences in functional improvements were identified between patients who selected unilateral versus bilateral TKR, indicating no recommendation for one procedure over the other.Electronic supplementary materialThe online version of this article (10.1186/s12891-018-2006-x) contains supplementary material, which is available to authorized users.

Background: Premenstrual syndrome (PMS) is a multifactorial disorder caused by hormone and autonomic imbalance. In our study, hyperglycemia-induced insulin secretion increased progesterone secretion and progressive autonomic imbalance. The young patients with diabetes mellitus (DM) revealed hypo-parasympathetic function and hypersympathetic function compared with nondiabetic controls. Young female patients with DM with higher blood sugar and autonomic malfunction may be associated with PMS. However, there is a lack of evidence about DM in females related to PMS. We evaluated female patients with DM who subsequently followed PMS in a retrospective cohort study. Methods: We retrieved data from the National Health Insurance Research Database in Taiwan. Female patients with DM between 20 and 50 years old were assessed by the International Classification of Disease, 9 Revision, Clinical Modification (ICD-9-CM) disease code of 250. Patients who were DM-free females were fourfold matched to the control group by age and disease index date. The ICD-9-CM disease code of 625.4 identified the incidence of PMS followed by the index date as events. The possible risk factors associated with PMS were detected with a Cox proportional regression. Results: DM was a significant risk factor for PMS incidence with an adjusted hazard ratio of 1.683 (95% confidence interval: 1.104–2.124, p < 0.001) in females after adjusting for age, other comorbidities, season, urbanization status of patients and the hospital status of visiting. Conclusion: This study noted an association between DM and PMS in female patients. Healthcare providers and female patients with DM must be aware of possible complications of PMS, aggressive glycemic control, decreased hyperglycemia and autonomic dysfunction to prevent this bothersome disorder.

Resistin and endothelin (ET)‐1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively. Although both hormones interact with each other, the exact signaling pathway of ET‐1 to act on resistin gene expression is still unknown. Using 3T3‐L1 adipocytes, we investigated the signaling pathways involved in ET‐1‐stimulated resistin gene expression. The upregulation of resistin mRNA expression by ET‐1 depends on concentration and timing. The concentration of ET‐1 that increased resistin mRNA levels by 100‐250% was approximately 100 nM for a range of 0.25~12 h of treatment. Treatment with actinomycin D blocked ET‐1‐increased resistin mRNA levels, suggesting that the effect of ET‐1 requires new mRNA synthesis. Treatment with an inhibitor of the ET type‐A receptor (ETAR), such as BQ610, but not with the ET type‐B receptor (ETBR) antagonist BQ788, blocked ET‐1‐increased the levels of resistin mRNA and phosphorylated levels of downstream signaling molecules such as ERK1/2, JNKs, AKT, and STAT3. Moreover, pretreatment of specific inhibitors of either ERK1/2 (U0126 and PD98059), JNKs (SP600125), PI3K/AKT (LY294002 and Wortmannin), or JAK2/STAT3 (AG490) prevented ET‐1‐increased levels of resistin mRNA and reduced the ET‐1‐stimulated phosphorylation of ERK1/2, JNKs, AKT, and STAT3, respectively. However, the p38 kinase antagonist SB203580 did not alter the effect of ET‐1. These results imply that ETAR, ERK1/2, JNKs, AKT, and JAK2, but not ETBR or p38, are necessary for the ET‐1 stimulation of resistin gene expression. In vivo observations that ET‐1 increased resistin mRNA and protein levels in subcutaneous and epididymal adipose tissues support the in vitro findings.

ObjectiveThis study was designed to investigate whether epigallocatechin gallate (EGCG) modulated the acute (30 min) and chronic (6 h) effects of endothelin (ET)‐1 on glucose uptake and glucose transporters in 3T3‐L1 adipocytes.MethodsGlucose uptake was assayed to measure the uptake of 3H‐2‐deoxyglucose. Western blot analysis was performed to measure levels of Gluts and ET‐1 signaling molecules.ResultsEGCG at 10 μM for 2 h was found to inhibit the acute effects of ET‐1 on glucose uptake and the translocation of glucose transporter (Glut)‐4 from the cytosol to the plasma membrane. EGCG had no effects on the translocation of Glut1 and total levels of Glut‐1 and Glut‐4 proteins. But, we observed that EGCG prevented the chronically ET‐1‐increased levels of glucose uptake and Glut‐1 protein expression, and it had no effects on the ET‐1‐altered levels of Glut‐1 and Glut‐4 translocation. The actions of ET‐1 were shown to be mediated through the extracellular signal‐regulated kinases (ERKs) and protein kinase B (PKB) pathways, but signaling was demonstrated to be prevented by EGCG pretreatment.ConclusionsThese data suggest that EGCG mediates the acute and chronic effects of ET‐1 on 3T3‐L1 adipocyte glucose uptake via the respective alteration of Glut‐4 translocation and Glut‐1 protein levels and via the ERK and PKB pathways.

Background and Objectives: Sepsis increases cardiovascular disease and causes death. Ischemic heart disease (IHD) without acute myocardial infarction has been discussed less, and the relationship between risk factors and IHD in septicemia survivors within six months is worthy of in-depth study. Our study demonstrated the incidence of IHD and the possible risk factors for IHD in septicemia patients within six months. Materials and Methods: An inpatient dataset of the Taiwanese Longitudinal Health Insurance Database between 2001 and 2003 was used. The events were defined as rehospitalization of stroke and IHD after discharge or death within six months after the first septicemia hospitalization. The relative factors of major adverse cardiovascular events (MACEs) and IHD were identified by multivariate Cox proportional regression. Results: There were 4323 septicemia survivors and 404 (9.3%) IHD. New-onset atrial fibrillation had a hazard ratio (HR) of 1.705 (95% confidence interval (C.I.): 1.156–2.516) for MACEs and carried a 184% risk with HR 2.836 (95% C.I.: 1.725–4.665) for IHD by adjusted area and other risk factors. Conclusions: This study explored advanced-aged patients who experienced more severe septicemia with new-onset atrial fibrillation, which increases the incidence of IHD in MACEs within six months of septicemia. Therefore, healthcare providers must identify patients with a higher IHD risk and modify risk factors beforehand.

(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case–control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren–Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78–1.20) and adjusted-OR: 0.90 (95% CI: 0.71–1.15) in allele model] in the present case–control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case–control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59–1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56–1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.